AJP - Heart and Circulatory Physiology, Vol 272, Issue 2 740-H747, Copyright © 1997 by American Physiological Society

ARTICLES

Canine pulmonary vasoreactivity to serotonin: role of protein kinase C and tyrosine kinase

S. A. Barman, J. R. Pauly and C. M. Isales
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta 30912, USA.

The role of protein kinase C- and protein tyrosine kinase-mediated signal transduction in the canine pulmonary vascular response to serotonin (5-HT) was determined in the isolated blood-perfused dog lung. Pulmonary vascular resistances and compliances were measured with vascular occlusion techniques. 5-HT (10(-5) M) significantly increased precapillary resistance by approximately 150% and postcapillary resistance twofold and significantly decreased total vascular compliance to approximately 50% of control values by decreasing large-vessel compliance and middle-compartment compliance. The 5-HT2-receptor blocker ketanserin (10(-7) M), the protein kinase C inhibitor staurosporine (10(-7) M), the voltage-dependent Ca2+-channel blocker verapamil (10(-5) M), and the specific protein tyrosine kinase inhibitors genistein (5 x 10(-4) M) and tyrphostin 25 (5 x 10(-4) M) completely inhibited the pressor response to 5-HT, whereas the 5-HT1-receptor antagonist (-)pindolol (10(-7) M) had no significant effect on the serotonergic response. These results indicate that the canine pulmonary vascular response to 5-HT involves activation of 5-HT2 receptors and suggests that this receptor signal transduction pathway involves protein kinase C and tyrosine kinase and the activation of voltage-dependent Ca2+ channels.

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